Interleukin-6, a kind of cytokine, is a protein that is involved in a variety of biological activities, including immunity. In general people, interleukin-6 is present in blood at a concentration as low as 1 pg/ml and acts as a regulator important for vital phenomena. It is known that, if interleukin-6 is present in excessive amounts in vivo, it causes autoimmune diseases and tumors. It was reported that a typical disease caused by interleukin-6 is rheumatoid arthritis and that the concentration of interleukin-6 in the blood of patients having this disease is significantly higher than that in healthy people. It was reported that antibodies that bind specifically to interleukin-6 present in excessive amounts can inhibit the activity of interleukin-6, thereby exhibiting therapeutic effects on various diseases. Thus, a number of multinational pharmaceutical companies have made many efforts to develop monoclonal antibodies that can inhibit the binding between interleukin-6 and interleukin-6 receptor to inhibit signaling therebetween. Among them, the multinational pharmaceutical company Roche and the Japanese pharmaceutical company Chugai succeeded in the development of the therapeutic antibody Tocilizumab (trade name: ACTEMRA therapeutic antibody) that can bind to interleukin-6 receptor to inhibit the signaling of interleukin-6. This therapeutic antibody was approved by the FDA and is currently marketed as an agent for treating rheumatoid arthritis. In addition, a variety of therapeutic antibody candidates have entered clinical trials to evaluate the therapeutic effects thereof.
However, antibodies have problems, including low tissue penetration ability due to their high molecular weights, and high product costs due to complex production processes. For this reason, studies on new protein backbones capable of substituting for antibodies have recently been actively conducted. As a result, a protein, named “repebody”, was developed. The repebody is a polypeptide prepared by fusing the N-terminus of internalin B having a leucine-rich repeat (LRR) structure with VLR based on the structural similarity therebetween so as to have a consensus design. The repebody is highly expressed in E. coli in the form of water-soluble monomer, and thus can reduce production costs. Also, it has high physical and chemical stabilities, and thus is easily modified. In addition, it is a novel protein backbone that has not been studied and developed, and thus is advantageously distinct from existing patents.
Under this background, the present inventors have made extensive efforts to develop repebody into a general-use binding protein backbone having a binding affinity for various proteins, and as a result, have selected a novel protein having a binding affinity for interleukin-6 based on a random mutation library constructed based on the analysis of the structural characteristic (modularity) and overall structure of repebody. In addition, the present inventors have prepared and selected a novel polypeptide (repebody) having a higher binding affinity for interleukin-6 through a repeat module-based affinity amplification method or a beneficial mutation predicted based on a protein complex structure, and have found that the repebody can prevent or alleviate cancer, thereby completing the present invention.